ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.50C>T (p.Thr17Ile) (rs138979875)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532549 SCV000630711 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 17 of the SDHB protein (p.Thr17Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs138979875, ExAC 0.004%). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 459151). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001023538 SCV001185437 uncertain significance Hereditary cancer-predisposing syndrome 2020-05-29 criteria provided, single submitter clinical testing The p.T17I variant (also known as c.50C>T), located in coding exon 1 of the SDHB gene, results from a C to T substitution at nucleotide position 50. The threonine at codon 17 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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